Circular RNAs in rat models of cardiovascular and renal diseases

Circular RNAs (circRNAs) have emerged as an important new class of genomic regulatory molecules contributing to the development of various diseases, but their relevance to the development and progression of hypertension remains largely unknown. A major impediment to begin studying circRNAs in rat models of inherited hypertension is that the rat as a valuable model of human diseases lags far behind the mouse and human in providing knowledge on circRNAs. In this study, a genome-wide circRNA profiling was performed from four rat strains that are widely used in hypertension research: the Dahl salt-sensitive rat (S), the Dahl salt-resistant rat (R), the spontaneously hypertensive rat (SHR), and the Wistar Kyoto rat (WKY). Combined hybridization data obtained from these four strains allowed for the identification of 12,846 circRNAs as being expressed in the rat kidneys. Out of these, 318 and 110 circRNAs were differentially expressed with a fold change > 1.5 (P < 0.05) in S vs. R and SHR vs. WKY, respectively. Among these circRNAs, circRNA/microRNA interaction was predicted since circRNAs are known as microRNA sponges to sequester microRNAs. Several circRNAs were further validated by quantitative real-time PCR. To our knowledge, our study is the primary report of profiling circRNAs in renal tissue and illustrates that circRNAs could be candidate genetic factors controlling blood pressure.